**15. Conclusion**

The development of resistance against antibacterial drugs is the rising challenge of the century, because it was nearly one century ago that bacterial infections were dealt a lethal blow by the discovery of antibiotics, which are now facing a drastic decline in efficacy against bacterial and fungal infections, due to the development of resistance. Generally, nanomaterial-mediated targeted drug delivery is a major thrust against antibacterial drug resistance. It has been noted that the development of resistance against PDT is a difficult feat for microbial pathogens to mount. It follows therefore that nanomaterial-mediated targeted PS delivery further diminishes the likelihood of the development of resistance. The boundaries may be pushed even further by the combination of nanomaterial-mediated delivery of antibiotic drugs and PDT PS, contained in multifunctional nanoconjugate systems used in photodynamic-antibiotic chemotherapy drug combination therapies because such systems would dramatically reduce systemic release of the antibiotic chemotherapy drug and PS. It is for these reasons that the ruthenium polypyridyl complexes, which are potent generators of ROS upon photoirradiation as antibacterial PDT PSs, have been developed with the purpose of pursuing the capability of combating antibiotic resistance [128]. In the same way as combining different antibiotic drugs is effective in repurposing older drugs rendered unusable by the development of resistance, so is combining antibiotic drugs with PDT [129].

Future benefits of combination therapies include enhancement of the combating of cancer and bacterial infections. However, the current rapid expansion of the scope of these combination therapies has left a few gaps. For example, the applications of the combination of MH with PDT, which appears to have been thwarted by the requirements for onerous investments in equipment and infrastructure, could benefit in the future from the development of handheld MH devices, subject to the advances in availability of such devices [125]. Therefore, this paper is a timeous addition to the advocacy for the development of such handheld devices. Additionally, other combinations with PDT hold great promise for the future, which are still being explored in experimental research. For example, the combination of PDT with cold atmospheric pressure plasma therapy has been shown by researchers at the Universität Greifswald in Germany, to eradicate bacterial infections of common skin and wound pathogens *in vitro* [130]. This provides an initial proof of concept for what could potentially revolutionize the way in which wound infections are treated in the future, especially in the developing world where such infections unnecessarily kill many people. Therefore, more research is needed to evaluate the combination of PDT

with CAP. The applicability of the folate antimicrobial targeting mechanisms across the microbial spectrum should also be determined. In conclusion, this paper has not only navigated the combination therapies that include PDT but also exposed some of the opportunities for further research and potential human benefit from it. The data show that the combinations of PDT with similarly minimally invasive technologies will further enhance the clinical translation of PDT and the development of devices that will support these combinations. Therefore, this paper encourages further research and innovation in the development of devices to be used in support of the research on combination therapies as well as clinical applications.
